Intraventricular GLP-1 reduces short- but not long-term food intake or body weight in lean and obese rats.
Glucagon-like-peptide-1 (7-36) amide (GLP-1), when infused into the third ventricle (I.V.T.), reduces short-term food intake. In the present experiments, we assessed whether I.V.T. administration of GLP-1 could influence long-term food intake and body weight of lean Long Evans rats and of fatty Zucker (fa/fa) rats. In Experiment 1, we replicated the observation that 10 microg GLP-1, given I.V.T., reduces one and 2 h food intake, and extended the observation to fatty Zucker rats. However, in both rat strains, 24 h food intake and body weight were unchanged by this acute treatment. In Experiment 2, GLP-1 (30 microg/day) was infused I.V.T. continuously for 4 days via an osmotic mini-pump. This treatment also had no effect on food intake or body weight in either Long-Evans or fatty Zucker rats. A control experiment verified that the GLP-1 remained biologically active over the duration of the infusion period. In a final experiment, Long-Evans rats were restricted to two 2 h periods of access to food each day for 6 days. Prior to each of these access periods, rats received either 15 microg of GLP-1 I.V.T. or a vehicle control injection. While GLP-1 significantly reduced food intake on the first day of treatment, this effect of GLP-1 rapidly disappeared such that it was reduced on the second day and absent on the third day; and there was no effect on body weight at any time. Collectively, the present experiments do not support the hypothesis that GLP-1, acting in the CNS, is an important regulator of long-term food intake and body weight.
Donahey
J C
JC
Program in Neurobiology and Behavior, University of Washington, Seattle 98195, USA.
van Dijk
G
G
Woods
S C
SC
Seeley
R J
RJ
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D002552:Cerebral Ventricles; D005247:Feeding Behavior / Q000187:drug effects*; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D015918:Infusion Pumps, Implantable; D008297:Male; D009765:Obesity / Q000188:drug therapy*; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D013997:Time Factors
D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon